title: Injectable small intestine submucosal extracellular matrix in an acute myocardial infarction model.
abstract: BACKGROUND
  The mechanisms involved in myocardial regeneration and cardiac remodeling were examined by injecting porcine-derived small intestine submucosal extracellular matrix (SIS-ECM), with and without circulating angiogenic cells (CACs), in a mouse model of acute myocardial infarction (MI).
  
  
  METHODS
  Nine- to 10-week-old female C57BL/6J mice had the left anterior descending (LAD) coronary artery ligated. Seven days after ligation, 38 randomly allocated animals received echocardiographically guided intramyocardial injections of phosphate buffered saline (PBS), CACs, SIS-ECM, or SIS-ECM + CACs. Repeated echocardiography and immunohistochemical analysis were performed at 28 days after ligation.
  
  
  RESULTS
  Baseline postligation left ventricular ejection fraction (LVEF) was equivalent in all groups. Twenty-one days after treatment, ejection fraction improved in the SIS-ECM + CAC treatment group (by 38% ± 2.12%) and the SIS-ECM treatment group (by 36% ± 3.71%), compared with the CAC-alone and PBS treatment groups (p < 0.1). Masson's trichrome staining showed reduced infarct size in SIS-ECM + CACs (34.2% ± 3.1%) and SIS-ECM alone (34.5% ± 4.7%) compared with CACs alone (47.3% ± 6.0%) and PBS (61.9% ± 5.5%; p < 0.002). Arteriolar density in periinfarct regions was enhanced in both SIS-ECM-treated groups (by ≥ 78% ± 7%; p = 0.03). More GATA4- and β-catenin-positive cardiac cells were found in the myocardium of SIS-ECM-treated animals.
  
  
  CONCLUSIONS
  Intramyocardial delivery of SIS-ECM 7 days after MI in a mouse model reduced infarct size and improved myocardial vessel density and function; when combined with CACs it helped restore myocardial cellularity, suggesting a potential therapeutic role for SIS-ECM in cardiac regeneration.
authors.affiliation: Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, Ontario, Canada.
authors.forename: Hadi Daood
authors.initials: HD
authors.lastname: Toeg
authors.forename: Rashmi
authors.initials: R
authors.lastname: Tiwari-Pandey
authors.forename: Richard
authors.initials: R
authors.lastname: Seymour
authors.forename: Ali
authors.initials: A
authors.lastname: Ahmadi
authors.forename: Suzanne
authors.initials: S
authors.lastname: Crowe
authors.forename: Branka
authors.initials: B
authors.lastname: Vulesevic
authors.forename: Erik J
authors.initials: EJ
authors.lastname: Suuronen
authors.forename: Marc
authors.initials: M
authors.lastname: Ruel
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005109:Extracellular Matrix; D005260:Female; D006321:Heart / Q000502:physiology; D007267:Injections; D007413:Intestinal Mucosa; D007421:Intestine, Small; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000628:therapy*; D012038:Regeneration; D013552:Swine
keywords: 30; CACs; FISH; LVEF; MI; PBS; SIS-ECM; circulating angiogenic cells; fluorescence in situ hybridization; left ventricular ejection fraction; myocardial infarction; phosphate buffered saline; small intestine submucosal extracellular matrix; α-SMA; α-smooth muscle actin